title: Transforming growth factor β-transduced mesenchymal stem cells ameliorate experimental autoimmune arthritis through reciprocal regulation of Treg/Th17 cells and osteoclastogenesis.
abstract: OBJECTIVE
  Bone marrow-derived mesenchymal stem cells (MSCs) can prevent various autoimmune diseases. We examined the therapeutic potential of transforming growth factor β (TGFβ)-transduced MSCs in experimental autoimmune arthritis, using an accepted animal model of collagen-induced arthritis (CIA).
  
  
  METHODS
  DBA/1J mice with CIA were treated with syngeneic TGFβ-induced MSCs, whereas control mice received either vehicle or MSCs alone. Arthritis severity was assessed by clinical and histologic scoring. TGFβ-transduced MSCs were tested for their immunosuppressive ability and differential regulation in mice with CIA. T cell responses to type II collagen were evaluated by determining proliferative capacity and cytokine levels. The effects of TGFβ-transduced MSCs on osteoclast formation were analyzed in vitro and in vivo.
  
  
  RESULTS
  Systemic infusion of syngeneic TGFβ-transduced MSCs prevented arthritis development and reduced bone erosion and cartilage destruction. Treatment with TGFβ-transduced MSCs potently suppressed type II collagen-specific T cell proliferation and down-regulated proinflammatory cytokine production. These therapeutic effects were associated with an increase in type II collagen-specific CD4+FoxP3+ Treg cells and inhibition of Th17 cell formation in the peritoneal cavity and spleen. Furthermore, TGFβ-transduced MSCs inhibited osteoclast differentiation.
  
  
  CONCLUSIONS
  TGFβ-transduced MSCs suppressed the development of autoimmune arthritis and joint inflammation. These data suggest that enhancing the immunomodulatory activity of MSCs and modulating T cell-mediated immunity using gene-modified MSCs may be a gateway for new therapeutic approaches to clinical rheumatoid arthritis.
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, and Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Hyun-Sil
authors.initials: HS
authors.lastname: Park
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Hye-Joa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Young-Gue
authors.initials: YG
authors.lastname: Cho
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Min
authors.forename: Byung-Ha
authors.initials: BH
authors.lastname: Chung
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Lee
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D010010:Osteoclasts / Q000276:immunology*; D010529:Peritoneal Cavity; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta